The present invention relates to a dispensing assembly for liquid droplets of the type comprising a dispenser, having a main bore communicating with the nozzle having a nozzle bore terminating in a dispensing tip and delivery means for moving liquid to the dispenser and from there through the bore to form a droplet on the exterior of the tip and then to cause a droplet to fall off therefrom. The invention is further concerned with a method of dispensing a droplet from a pressurised liquid delivery source through a metering valve dispenser comprising an elongate body member having a main bore communicating through a valve seat with a nozzle having a nozzle bore terminating in a dispensing tip, a separate floating valve boss of magnetic material housed in the body member, the cross sectional area of which is sufficiently less than that of the main bore to permit the free passage of liquid therebetween thus by passing the valve boss; and a separate valve boss actuating coil assembly surrounding the body member.
The present invention is generally related to liquid handling systems and in particular to systems for dispensing and aspirating of small volumes of reagents. It is particularly directed to a high throughput screening, polymerase chain reaction (PCR), combinatorial chemistry, microarraying, medical diagnostics and others. In the area of high throughput screening, PCR and combinatorial chemistry, the typical application for such a fluid handling system is in dispensing small volumes of the reagents, e.g. 1 ml and smaller and in particular volumes around 1 microliter and smaller. It is also directed to the aspiration of volumes from sample wells so that the reagents can be transported between the wells. The invention relates also to microarray technology, a recent advance in the field of high throughput screening. Microarray technology is being used for applications such as DNA arrays. In this technology the arrays are created on glass or polymer slides. The fluid handling system for this technology is directed to dispensing consistent droplets of reagents of submicrolitre volume.
Development of instrumentation for dispensing of minute volumes of liquids has been an important area of technological progress for some time. Numerous devices for controlled dispensing of small volumes of liquids (in the range of 1 xcexcl and smaller) for ink jet printing application have been developed over the past twenty five years. More recently, a wide range of new areas of applications has emerged for devices handling liquids in the low microlitre range. These are discussed for example in xe2x80x9canalytical chemistryxe2x80x9d [A. J. Bard, Integrated chemical systems, Wiley-Interscience Pbl, 1994], and xe2x80x9cbiomedical applications [A. G. Graig, J. D. Hoheeisel, Automation, Series Methods in Microbiology, vol 28, Academic Press, 1999].
The present invention is also directed to medical diagnostics e.g. for printing reagents on a substrate covered with bodily fluids for subsequent analysis or alternatively for printing bodily fluids on substrates.
The requirements of a dispensing system vary significantly depending on the application. For example, the main requirement of a dispensing system for the ink jet applications is to deliver droplets of a fixed volume with a high repetition rate. The separation between individual nozzles should be as small as possible so that many nozzles can be accommodated on a single printing cartridge. On the other hand in t his application the task is simplified by th e fact that the mechanical properties of the liquid dispensed namely ink are well defined and consistent. Also in most cases the device used in the ink jet applications does not need to aspire the liquid through the nozzle for the cartridge refill.
For biomedical applications such as High Throughput Screening (HTS) the requirements imposed on a dispensing system are completely different. The system should be capable of handling a variety of reagents with different mechanical properties e.g. viscosity. Usually these systems should also be capable of aspiring the reagents through the nozzle from a well. On the other hand there is no such a demanding requirement for the high repetition rate of drops as in ink jet applications. Another requirement in the HTS applications is that cross contamination between different wells served by th e same dispensing device be avoided as much as possible.
The most common method of liquid handling for the HTS applications is based on a positive displacement pump such as described in U.S. Patent Specification No. U.S. Pat. No. 5,744,099 (Chase et al). The pump consists of a syringe with a plunger driven by a motor , usually a stepper or servo-motor. The syringe is usually connected to the nozzle of the liquid handling system by means of a flexible polymer tubing The nozzle is typically attached to an arm of a robotic system which carries it between different wells for aspiring and dispensing the liquids. The syringe is filled with a liquid such as water. The water continuously extends through the flexible tubing into the nozzle down towards the tip. The liquid reagent which needs to be dispensed, fills up into the nozzle from the tip. In order to avoid mixing of the water and the reagent and therefore cross-contamination, an air bubble or bubble of another gas is usually left between them. In order to dispense the reagent from the nozzle, the plunger of the syringe is displaced. Suppose this displacement expels the volume xcex94V of the water from the syringe. The front end of the water filling the nozzle is displaced along with it. The water is virtually incompressible. If the inner volume within the flexible tubing remains unchanged, then the volume xcex94V displaced from the syringe equals the volume displaced by the moving front of the water in the nozzle. If the volume of the air bubble is small it is possible to ignore the variations of the bubble""s volume as the plunger of the syringe moves. Thus the back end of the reagent is displaced by the same volume xcex94V in the nozzle, and therefore the volume ejected from the tip is the same xcex94V. This is the principle of operation of such a pump. The pump works accurately if the volume xcex94V is much greater than the volume of the air bubble. In practice the volume of the air bubble changes as the plunger of the syringe moves. Indeed in order to eject a drop from the tip, the pressure in the tubing should exceed the atmospheric pressure by an amount determined by the surface tension acting on the drop before it detaches from the nozzle. Therefore at the moment of ejection the pressure in the tubing increases and after the ejection, it decreases. As common gasses are compressible, the volume of the air or gas bubble changes during the ejection of the droplet and this adds to the error of the accuracy of the system. The smaller the volume of the air bubble, the smaller is the expected error. In other words the accuracy is determined significantly by the ratio of the volumes of the air bubble and the liquid droplet. The smaller this ratio is the better the accuracy. For practical reasons it is difficult to reduce the volume of the air or gas bubble to below some one or two microlitres and usually it is considerably greater than this. Therefore, this method with two liquids separated by an air or gas bubble and based on a positive displacement pump is not well suited for dispensing volume as low as 1 microlitre or lower. There are also additional limitations on accuracy when sub-microlitre volumes need to be dispensed. For example, as the arm of the robotic system moves over the target wells, the flexible tubing filled with the water bends and consequently its inner volume changes. Therefore, as the arm moves, the front end of the water in the nozzle moves to some extent even if the plunger of the syringe does not. This adds to the error of the volume dispensed. Other limitations are discussed in Graig et al referred to above. Examples of such positive displacement pumps are shown in U.S. Pat. Specification No. 5,744,099 (Chase et al). Similarly the problems of dispensing drops of small volume are also described and discussed in U.S. Pat. Specification No. 4,574,850 (Davis) and U.S. Pat. No. 5,035,150 (Tomkins).
U.S. Pat. Specification No. 5,741,554 (Tisone) describes another method of dispensing small volumes of fluids for biomedical application and in particular for depositing the agents on diagnostic test strips. This method combines a positive displacement pump and a conventional solenoid valve. The positive displacement pump is a syringe pump filled with a fluid to be dispensed. The pump is connected to a tubing. At the other end of the tubing there is a solenoid valve located close to the ejection nozzle. The tubing is also filled with the fluid to be dispensed. In this method the piston of the pump is driven by a motor with a well defined speed. This speed determines the flow rate of the fluid from the nozzle provided the solenoid valve is opened frequently enough and the duty cycle open/close of the valve is long enough. The solenoid valve is actuated with a defined repetition rate. The repetition rate of the valve and the flow rate of the pump determine the size of each drop. For example, if the pump operates at a flow rate of 1 xcexcl per second and the repetition rate is 100 open-close cycles per second, then the size of each drop is 10 nl, However, for dispensing of submicrolitre volumes for HTS applications this method is often inappropriate since it is required to aspire fluid through the nozzle in small quantities and then dispense it in fractions of this quantity. To avoid mixing of the fluid aspired with the one in the syringe pump, it is probably necessary to place a bubble of gas in the tube with the attendant problems described above.
While this type of pump and solenoid valve is designed for dispensing series of drops of consistent size, it may not be well suited for dispensing single drops i.e. one drop on demand which is exactly the mode of dispensing used in the HTS applications. If the solenoid valve open time and/or operating frequency are too small for a given pump flow rate, the pressure in the dispenser will become too great, causing possible rupture or malfunctioning of the system.
U.S. Pat. No. 5,758,666 (Carl O. Larson, Jr. et al) describes a surgically implantable reciprocating pump having a floating piston made of a permanent magnetic material and incorporating a check valve. The piston can be moved by means of energising the coils in a suitable timing sequence. The piston allows the flow of liquid through it when it moves in one direction as the check valve is open and when it moves in the opposite direction, the check valve is closed and the liquid is pumped by the piston.
U.S. Pat. No. 4,541,787 (Sanford D. DeLong) describes an electromagnetic reciprocating pump with a xe2x80x9cmagnetically responsivexe2x80x9d piston as it contains some ferromagnetic material. The piston is actuated by at least two coils located outside the cylinder containing the piston. The coils are energised by a current with a required timing.
Drops of microliter volume and smaller can be also generated by the method of electrospray which is mainly used for injection of a fluid into a chemical analysis system such as a mass spectrometer. In most cases the desired output of electrospray is not a stream of small drops but rather of ionised molecules. The method is based on supplying a liquid under pressure through a capillary towards its end and then a strong electrostatic field is generated at the end of the capillary by applying a high voltage, typically over 400V, between the end of the capillary and a conductor placed close to it. A charged volume of fluid at the end of the capillary is repelled from the rest of the capillary by Coulomb interaction as they are charged with the like charges. This forms a flow of charged particles and ions in the shape of a cone with the apex at the end of the capillary. A typical electrospray application is described in U.S. Pat. Specification No. 5,115,131 (James W. Jorgenson et al). There are inventions where the droplets emitted from a capillary are charged in order to prevent them from coming together with coagulation. This approach is described in U.S. Pat. No. 5,891,212 (Jie Tang et al) for fabrication of uniform charged spheres. U.S. Pat. No. 4,302,166 (Mack J. Fulwyler et al) teaches how to handle uniform particles each containing a core of one liquid and a solidified sheath. In this invention the electric field is applied in a similar way to keep the particles away from each other until the sheath of the particles has solidified. In this invention the particles are formed from a jet by applying a periodic disturbance to the jet. U.S. Pat. No. 4,956,128 (Martin Hommel et al) teaches how to dispense uniform droplets and convert these into microcapsules. A syringe pump supplies the fluid into a capillary. A series of high voltage pulses is applied to the capillary. The size of the droplets is determined by the supply of fluid through the capillary and the repetition rate of the high voltage pulses. The patent discusses generation of a single drop on demand. U.S. Pat. No. 5,639,467 (Randel E. Dorian et al) teaches a method of coating of substrates with a uniform layer of biological material. A droplet generator is employed which consists of a pressurised container connected to a capillary. A high constant voltage is applied between the capillary and the receiving gelling solution.
There are numerous methods for ink jet dispensing. The ink jet printing industry is the main driving force in the continuing progress in this field. Some of the well known methods are listed below:
a) One of the oldest methods of creating separated and uniform droplets is based on breaking a jet of liquid emerging from the nozzle. To control the breaking up of the jet into separated droplets periodical vibrations are applied to the jet of liquid. The optimal frequency F of such vibrations was estimated by Lord Rayleigh over a hundred years ago:   F  =      V          4.51      ⁢      d      
xe2x80x83where
Vxe2x80x94emerging jet velocity
dxe2x80x94jet diameter.
All droplets at this frequency are created uniformly with the same volume. A typical example of implementation of this method can be found in U.S. Pat. No. 5,741,554 (Tissone).
b) In numerous implementations of ink jet printing, pressure waves inside a liquid-holding chamber are created by a piezoelectric actuator. Accelerated by pressure waves, the liquid in the chamber achieves sufficient speed to move through the nozzle and to overcome capillary forces at the tip. In such a case a small droplet will be formed.
c) According to one method, the piezoelectric transducer changes the volume of the container and creates pressure waves in the liquid in the container. The action of compression wave causes some amount of the liquid (ink) to go through the nozzle and to form droplets which are separated from the bulk liquid in the container, see for example U.S. Pat. No. 5,508,726 (Sugahara).
d) In U.S. Pat. No. 5,491,500 (Inui) an ink jet head is described where liquid in the printing head is xe2x80x9cpushedxe2x80x9d by progressive waves created by a synchronized row of piezoelectric devices. Eventually, liquid in the printing head obtains enough speed to spray sequences of droplets through the nozzle.
In the methods b) to d) listed above it is necessary to have liquid without vapor and bubbles. Droplet viscosity, surface tension are very important. In the b) and c) cases droplets can be only of a fixed size.
In summary, the most common method of handling reagents used in HTS applications is based on a positive displacement pump and a gas bubble. The problem is that when dispensing volumes of reagents around 1 microliter or smaller the variation in the volume of the bubble during the dispensation compromises the accuracy. It has been found difficult to eject small droplets of precisely required volume using this method.
The use of a solenoid valve has two main disadvantages when used for HTS applications. The first one is the relatively high cost of a solenoid valve such that it cannot be a disposable element and thus cross contamination can be a major problem. Further difficulties have been experienced in achieving dead volumes smaller than 1 to 2 microliters in a conventional solenoid valve.
Piezo dispensers while used are often not well suited for dispensing reagents for medical applications. The reason is that the piezo dispenser commonly requires that fluid to be dispensed has well defined and consistent properties. Unfortunately, reagents and bodily fluids used in medical and biomedical applications have broadly varying properties and often contain particles and inhomogenities which can block the nozzle of the piezo dispenser.
As the size of wells becomes smaller and smaller, the problem of missing the correct well or dropping the liquid reagent at the wrong place of the substrate on which the reagent is being deposited becomes more and more significant. Measurement of the volume of the drops dispensed in the submicrolitre range is a formidable task. It would be a highly desired and valuable feature of a liquid handling instrument to be capable of measurement of volume of individual droplets especially in the submicroliter range, and also measurement of the dispensation event which will allow excluding missing a drop.
U.S. Pat. No. 5,559,339 (Domanik) teaches a method for verifying a dispensing of a fluid from a dispense nozzle. The method is based on coupling of electromagnetic radiation which is usually light from a source to a receiver. As a droplet of fluid travels from the nozzle it obstructs the coupling and therefore the intensity of the signal detected by the receiver is reduced. The mechanism of such an obstruction is absorption of electromagnetic radiation by the droplet. The disadvantage of this method is that the smaller the size of the droplet, the smaller is the absorption in it. Almost certainly the method should not work for fluids which do not absorb the radiation.
For a range of applications such as high through put screening where minute droplets of fluids with a broad range of optical properties need to be dispensed the methods disclosed in this specification are inappropriate. Further the specification acknowledges that it will only operate satisfactorily with major droplets.
The present invention is directed towards providing an improved method and apparatus for dispensing of volumes of liquids as small as 10 nl=10xe2x88x928 l or even smaller, while at the same time it should be possible to dispense larger droplets such as those as large at 10 microliters or even greater.
Another objective is to provide a method where the quantity of the fluid dispensed can be freely selected by the operator and accurately controlled by the dispensing system. The system should be capable of dispensing e.g. a 10 nl drop followed by a 500 nl one in comparison to for example ink jet printing where the volume of one dispensation is fixed, and dispensations are only possible in multiples of this quantity.
The invention is also directed towards providing a method where the fluid can be dispensed on demand, i.e. one quantity can be dispensed at a required time as opposed to a series of dispensations with periodic time intervals between them. Yet, the method should also allow for dispensation of doses with regular intervals between subsequent dispensations, for example, printing with reagents.
Another objective of the present invention is to provide a method and a device suitable for dispensing a fluid from a supply line to a sample well and also for aspiring a fluid from the sample well into the supply line. The device should be able to control accurately the amount of the fluid aspired into the nozzle of the dispenser from a supply well.
Another objective is to provide a low cost front end of the dispensing device called herein the dispenser which could be disposed of when it becomes contaminated namely the part which comes in direct contact with the reagents dispensed. It is an important objective of the invention to provide a dispenser such that the disconnection and replacement is achieved simply such as by an arm of a robot.
Another objective is to provide a method for handling fluids in a robotic system for high throughput screening or microarraying which would be suitable for accurate dispensing and aspiring volumes smaller than the ones obtainable with current positive displacement pumps.
Yet another objective is to provide means of more accurate delivery of a drop of liquid reagent to a correct target well on a substrate and also to improve the accuracy of delivery of the drop to a correct location in a well forming part of a receiving substrate. Yet another objective is to provide means for directing the doses of fluids into different wells of a sample well plate and means of controlling the delivery address of the dose on the sample well plate to speed up the liquid handling procedure.
Yet another objective of the invention is to reduce xe2x80x9csplashingxe2x80x9d as the drop arrives at the well.
Another objective of the invention is to provide information if the drop was dispensed or not. It is additional an objective to measure the volume of the drop which was dispensed.
According to the invention there is provided a dispenser for discrete droplets of less than ten microlitres (10 xcexcl) in volume of a liquid comprising:
(A) a main assembly;
(B) a liquid container comprising:
an elongate body member having a straight main bore;
an inlet to the main bore;
a valve seat in the body member forming a main bore outlet remote from and substantially in line with the inlet;
a nozzle mounted on the body member and having a nozzle bore communicating with the valve seat;
a droplet dispensing tip on the nozzle remote from the valve seat;
a separate floating valve boss of magnetic material loosely mounted in the main bore, its cross-sectional area relative to that of the main bore being such as to permit the free flow of liquid between the main bore inlet and outlet by passing the valve boss, said valve boss not being mechanically connected to the body member;
(C) means for releasably securing the liquid container to the main assembly;
(D) means for exerting a pressure differential on the liquid in the dispenser; and
(E) a separate valve boss actuating assembly adjacent the body member for applying an electromagnetic force to the valve boss to engage and disengage the valve boss from the valve seat.
The invention is particularly directed towards the dispensing of droplets within the range 1 nanoliter (1 nl) to 10 microliters (10 xcexcl). The smaller the droplet, the more difficult the dispensing becomes.
This has major advantages in that the dispensing assembly does not rely on a positive displacement pump, or any other pressurised source for the actual delivery, it uses what is effectively a solenoid valve, but a solenoid valve that is not of conventional construction. All it needs is a pressurised liquid delivery which can be any form of pressurised liquid delivery such as a positive displacement pump which functions as a source of pressure, not a metering device. It is important to appreciate that there is no mechanical connection between the valve boss and the other parts of the dispenser. There are no springs, nor any other mechanical actuation means. In fact there is virtually no dead volume in the dispenser. It will also be appreciated that the dispenser is effectively separate from the actuating coils so that a very low cost dispenser can be used which will allow easy removal. A major feature of the invention is that the elongate body member of the dispenser is effectively disposable.
In one embodiment of the invention the valve boss is of a hard magnetic material and indeed with this latter embodiment ideally the valve boss is biased to a closed position into engagement with the valve seat by an external magnetic field generated by the actuating coil assembly. This is in direct contradiction to more conventional solenoid valves, where the plunger is usually of a soft magnetic material. It has been found that for dispensing minute volumes the force that can be exerted by the valve boss by a current coil is greater with a hard magnetic material and thus the valve boss moves quicker and greater accuracy of dispensing is achieved. With a hard magnetic material only one coil is necessary as all that is required is to reverse the direction of the current to open and close the valve.
Ideally the valve boss is covered with a layer of a soft polymer material. This will ensure that there is a good seal at the valve seat. Alternatively the value boss may be made from flexible bonded magnetic material
In one embodiment of the invention the actuating coil assembly comprises two separate sets of coils for moving the boss in opposite directions within the body member. Two coils are obviously necessary when the valve boss is made of a soft magnetic material.
Ideally the valve boss, the body member and nozzle form the one separate sub assembly releasably detachable from the remainder of the dispenser. This provides greater disposability and, with greater disposability cross-contamination may be effectively eliminated which is of paramount importance for medical and biological applications.
In one embodiment of the invention the actuating coil assembly comprises a source of electrical power and a controller for varying the current over time as each droplet is being dispensed. Varying the current ensures that the peak current is supplied when required i.e. when actually opening and closing the valve, while by varying the current and only using the highest current when required, overheating is prevented and as will be appreciated the use of current of a higher current value when required is acceptable and useful.
Ideally the boss is constructed for limited movement out of line with the main bore longitudinal axis. One advantageous shape is for the boss to be a cylindrical plug. This is particularly advantageous for hard magnetic materials in that axisymmetrical magnetization can be achieved.
In one embodiment of the invention the cylindrical plug has radially extending circumferential fins whereby on movement of the boss towards the valve seat liquid is urged into the nozzle bore and onto the tip. This ensures even more positive displacement of the liquid into the nozzle bore and thus more positive dispensing of the droplets. Such materials can either have hard or soft magnetic properties and if they are of a relatively soft polymer material they can improve the performance of the seal.
Ideally the body member and the nozzle form the one integral moulding of plastics material and integral moulding is relatively inexpensive and further improves disposability.
In one embodiment of the invention there is provided a dispensing assembly comprising;
an electrode incorporated in the dispensing tip;
a separate receiving electrode remote from the tip; and
a high voltage source connected to one of the electrodes to provide an electrostatic field therebetween.
It is often advantageous to decrease the pressure in the line connected to the dispenser as this will allow much easier pressure tight connections to be made and thus advantageously increase the disposability and replaceability of parts of the dispenser. Further because of the use of lower pressures the droplets are now ejected at lower speed at these lower pressures so that splashing is minimised. The electrostatic field still allows the dispenser to operate.
Ideally the receiving electrode is below the dispensing tip and a droplet receiving substrate may be mounted between the receiving electrode and the dispenser tip, or mounted below the receiving electrode, the receiving electrode in the latter case having at least one hole for the droplet to pass through to the receiving substrate. Indeed there may be a plurality of receiving electrodes at least one of which is activated at any one time. All of these improve the accuracy and control of the dispensing.
Ideally synchronous indexing means may be provided for the dispenser and/or the receiving electrode for accurate deployment of droplets on the substrate.
In one embodiment of the invention there is more than one receiving electrode forming droplet deflection electrodes which are mounted below the dispensing tip and above the droplets receiving substrate and in which the high voltage source has control means to vary the voltage applied to the deflection electrodes. All of these further improve the accuracy of the guidance of the droplets onto the receiving substrate. This has become particularly important with the miniaturisation of substrates since it becomes increasingly difficult to ensure that the droplet reaches its correct destination.
In one embodiment of the invention there is provided a detector for sensing the separation of the droplet from the dispensing tip. In a particularly preferred example of this latter embodiment, the detector comprises:
a source of electromagnetic radiation;
means for focussing the radiation on the end of the dispensing tip: and
means for collecting the radiation transmitted by a droplet on the dispensing tip. Preferably this is reflected or refracted radiation.
In many instances it is necessary to ensure that a droplet did indeed get dispensed.
In some of these embodiments the source of radiation is mounted within the dispenser nozzle.
Ideally means are provided for measuring the charge of the droplet which can be conveniently done in a Faraday Pail which can have a bottom or may be bottomless. This will allow both the charge and mass of the droplet to be ascertained and in particular when using the bottomless Faraday Pail the actual mass of the droplet can be ascertained without loss of liquid.
Further the invention provides a dispenser for discrete droplets of less than ten microliters (10 xcexcl) in volume of a liquid comprising:
(A) a main assembly;
(B) a liquid container comprising:
an elongate body member having a straight main bore;
an inlet to the main bore;
a valve seat in the body member forming a main bore outlet remote from the inlet;
a nozzle mounted on the body member and having a nozzle bore communicating with the valve seat;
a droplet dispensing tip on the nozzle remote from the valve seat;
(C) means for exerting a pressure differential on the liquid in the dispenser;
(D) a solenoid valve assembly mounted in the main bore of the elongate body member of the liquid container;
(E) an electrode incorporated in the dispensing tip;
(F) a separate receiving electrode remote from the tip; and
(G) a high voltage generating means connected to one of the electrodes with the other electrodes maintained at a different voltage to provide an electrostatic field therebetween.
Further the invention provides a method of dispensing a droplet having a volume less than ten micro liters (10 xcexcl) from a pressurised liquid delivery source through a metering valve dispenser comprising an elongate body member having a main bore communicating through a valve seat with a nozzle having a nozzle bore terminating in a dispensing tip, a separate floating valve boss of magnetic material housed in the body member, the cross sectional area of which is sufficiently less than that of the main bore to permit the free passage of liquid therebetween thus bypassing the valve boss; and a separate valve boss actuating coil assembly surrounding the body member, comprising the steps of:
delivering the pressurised liquid to the dispenser;
opening the valve by actuating the coil assembly for a preset time to deliver liquid around the valve boss into the nozzle bore; and
closing the valve as the droplet falls off.
In this latter method, the step may be performed of the valve being shut off of generating a pulse of voltage at a receiving electrode remote from the dispensing tip to generate an electrostatic field to cause an electrostatic potential between the droplet and the receiving electrode to detach it from the dispensing tip. This will allow the liquid to be pressurised at less than 4 or even 2 bar.
In this latter method the receiving electrode may be mounted beneath a droplet receiving substrate and the nozzle, or between a droplet receiving substrate and the nozzle. In either of these methods the electrode could move after each droplet is dispensed to direct the next droplet to another position on the substrate and further in any of these methods spaced apart deflection electrodes may be placed around the dispensing tip and a droplet receiving substrate and the electrodes are differentially charged to cause the droplet to move laterally as it drops from the dispensing trip. This ensures accurate placement of droplets on substrates. Indeed the deflection electrodes can be placed in many suitable places above or below the substrate all that is required is to deflect the droplet.
Further the invention provides a method comprising the steps of:
measuring the volume of a droplet of a particular liquid for different drop off voltages;
storing a database of the measurements;
recording the drop off voltage when a droplet detaches from the dispensing tip; and
retrieving the volume from the database.
This is a particularly suitable way of calibrating the device.
Preferably the drop off voltage is measured by a Faraday Pail.
When it is desired to record the drop-off of a droplet, this invention provides a method of so-doing which includes the steps of:
directing an electromagnetic beam from a source of electromagnetic radiation at the droplet as it forms at the tip; and
monitoring the electromagnetic radiation coupled by the droplet at a collector remote from the droplet.
In this latter method the light beam may be the source of electromagnetic radiation and the amount of light reflected and/or refracted by the droplet is monitored. This is a particularly convenient and relatively inexpensive way of providing the source of radiation.
In one method according to the invention the steps are performed of:
measuring the charge of droplets of a particular liquid for different volumes of droplets;
storing a database of the measurements;
recording the charge on each droplet; and
retrieving the volumes from the database.
This is a very suitable way of obtaining the mass and volume of the various liquids being dispensed.
A particularly suitable way of carrying out this method is by:
measuring the width of the voltage pulse in a Faraday pail;
determining the time taken for the droplet to pass through the pail;
deriving the speed of the droplet from the time taken to pass through the pail; and
calculating the mass of the droplet from the charge to mass ratio.
The great advantage of using a Faraday Pail is that there is no destruction or loss of any of the droplets.